Risk of systemic lupus erythematosus elevated years after testing positive for antinuclear antibodies: national cohort study in Denmark.

Abstract

The objective of this study was to assess the long-term risk of SLE following ANA positivity in a nationwide cohort. We followed ANA-tested, SLE-free individuals from 2000-2017 using national laboratory and health registers. ANA tests included ELISA-like CTD screening (ANA-CTD), single-dilution ANA (SDT-ANA) at dilution 1:160, and end-point ANA titre (EPT-ANA) at dilutions of 1:160-1:1280. In routine practice, ANA-CTD is often used in general practice, and SDT-ANA and EPT-ANA in secondary and tertiary care. Hazard ratios (HR) of SLE were estimated using Cox models, and 5-year cumulative incidence using Kaplan-Meier methods. Among 342 777 ANA-tested individuals, 647 developed SLE. ANA positivity was strongly associated with SLE. ANA-CTD positivity conferred the highest risk (HR 67.3, 95% CI 45.8-99.0), followed by SDT-ANA (HR 18.0, 95% CI 14.4-22.5). Homogeneous and speckled SDT-ANA patterns carried the greatest risk (HR 15.7 and 7.90), with 5-year cumulative incidences up to 9.18% and 5.29% for strongly positive ANA intensity. Risk was highest within the first year, but remained elevated beyond 5 years for homogeneous and speckled patterns. Absolute risks were highest in younger individuals (18-30 years), reaching 5-year cumulative incidences of 4.99% for ANA-CTD, 4.12% for SDT-ANA, and 15.0% for EPT-ANA. ANA positivity was associated with markedly elevated short-term and sustained long-term SLE risk, particularly in younger adults and individuals with high-intensity homogeneous or speckled patterns. Nonetheless, absolute risk remained low, highlighting the need to interpret ANA results within a broader clinical context, and caution against direct extrapolation to unselected primary care populations.